ANALYSIS OF THE UV-INDUCED MELANOGENESIS AND GROWTH ARREST OF HUMAN MELANOCYTES

Cultured human melanocytes derived from different skin types responded to frequent treatment with ultraviolet (UV) light with increased mela nin synthesis, decreased proliferation, and morphologic signs of aging . These effects were augmented by increased frequency of irradiation w ith 15.5 mJ/cm(2) UV light. Stimulation of melanogenesis by UV light i nvolved an increase in tyrosinase activity, without any change in the amounts of either tyrosinase or tyrosinase-related protein (TRP)-1, an d a decrease in the amount of TRP-2, as determined by Western blot ana lysis. These results are different from the mechanisms by which other melanogenic agents, such as cholera toxin and isobutyl methylxanthine, stimulated melanogenesis, whereby the amounts of tyrosinase, TRP-1 an d TRP-2 were increased. The decrease in the amount of TRP-2 might be s ignificant in that it might alter the properties of the newly synthesi zed melanin. The UV irradiation protocol that was followed blocked mel anocytes in G(2)-M phase of the cell cycle without compromising cellul ar viability. Following three rounds of UV irradiation, melanocytes co uld recover from the growth arrest and resume proliferation. Treatment with 0.1 mu M a-melanocyte stimulating hormone (alpha-MSH) postirradi ation enhanced the melanogenic effect of UV light and stimulated the m elanocytes to proliferate. The effects of alpha-MSH on the UV-induced responses and their implications on photocarcinogenesis are being furt her investigated. Analyzing the mechanisms by which UV light exposure affects normal melanocytes might lead to a better understanding of hen : these cells undergo malignant transformation, and why individuals wi th different skin types differ in their susceptibility to skin cancers .